Cyclodextrins in Drug Delivery Systems and Their Effects on Biological Barriers

L

Preformulation studies and bioavailability enhancement of curcumin with a ‘two in one’ PEG-β-cyclodextrin polymer

Drug delivery systems are used to improve the biopharmaceutical properties of curcumin. Our aim was to investigate the effect of a water-soluble ‘two in one’ polymer containing covalently bonded PEG and βCD moieties (βCPCD) on the solubility and bioavailability of curcumin and compare it to a polymeric β-cyclodextrin (βCDP) cross-linked with epichlorohydrin. Phase-solubility and dynamic light scattering (DLS) experiments showed that the solubility of curcumin increased significantly in 10 m/m % βCPCD and βCDP solutions, but βCPCD–curcumin particles had higher hydrodynamic volume. The formation of the βCPCD–curcumin complex in solution and sedimented phase was confirmed by NMR spectroscopy. Biocompatibility and permeability experiments were performed on Caco-2 cells. Polymers did not show cytotoxicity up to 10 m/m % and βCPCD significantly increased the permeability of curcumin. DLS measurements revealed that among the interaction of polymers with mucin, βCPCD formed bigger aggregates compared to βCDP. Curcumin complexes were lyophilized into capsules and structurally characterized by micro-CT spectroscopy. Drug release was tested in a pH 1.2 medium. Lyophilized complexes had a solid porous matrix and both βCPCD and βCDP showed rapid drug release. βCPCD provides an opportunity to create a swellable, mucoadhesive matrix system for oral drug delivery

Reduced miR-26b Expression in Megakaryocytes and Platelets Contributes to Elevated Level of Platelet Activation Status in Sepsis

L

Chrysin directing an enhanced solubility through the formation of a supramolecular cyclodextrin–calixarene drug delivery system: a potential strategy in antifibrotic diabetes therapeutics

Calixarene 0118 (OTX008) and chrysin (CHR) are promising molecules for the treatment of fibrosis and diabetes complications but require an effective delivery system to overcome their low solubility and bioavailability. Sulfobutylated β-cyclodextrin (SBECD) was evaluated for its ability to increase the solubility of CHR by forming a ternary complex with OTX008. The resulting increase in solubility and the mechanisms of complex formation were identified through phase-solubility studies, while dynamic light-scattering assessed the molecular associations within the CHR-OTX008-SBECD system. Nuclear magnetic resonance, differential scanning calorimetry, and computational studies elucidated the interactions at the molecular level, and cellular assays confirmed the system’s biocompatibility. Combining SBECD with OTX008 enhances CHR solubility more than using SBECD alone by forming water-soluble molecular associates in a ternary complex. This aids in the solubilization and delivery of CHR and OTX008. Structural investigations revealed non-covalent interactions essential to complex formation, which showed no cytotoxicity in hyperglycemic in vitro conditions. A new ternary complex has been formulated to deliver promising antifibrotic agents for diabetic complications, featuring OTX008 as a key structural and pharmacological component

Pharmacokinetic Properties of Fluorescently Labelled Hydroxypropyl-Beta-Cyclodextrin

L

Investigation of the endocytosis and its cellular effects of beta-cyclodextrin derivatives on intestinal epithelial cells

A ciklodextrinek a főként a gyógyszeriparban, de manapság egyre szélesebb körben az élelmiszeriparban, kozmetikai iparban is alkalmazott segédanyagok. A dolgozat a különböző béta-ciklodextrin származékok endocitózisának vizsgálatát mutatja be intesztinális epitél sejteken. Ezen vizsgálaton felül a ciklodextrinek autofágiára és NF- kappa B útvonalra gyakorolt hatásának vizsgálatát is. Kutatási eredményeink alapján elmondható, hogy a ciklodextrinek endocitózissal felvételre kerülnek a sejtekbe. Nem indukálják az NF-kappa B útvonalat, tehát nem indukálnak gyulladásos folyamatokat. A kontroll mintákhoz képest nem indukálják az autofagoszómák képződését.egységes, osztatlangyógyszerészmagyarnappalig